Rat Anti-Mouse Cd44 Heterohybridoma [LN225]

Objective To determine whether overexpression of the chitin degrading enzyme, chitotriosidase (CHIT1), modulates macrophage function and ameliorates atherosclerosis. Approach and Results Using a mouse model that conditionally overexpresses CHIT1 in macrophages (CHIT1-Tg) crossbred with theLdlr(-/-)mouse provided us with a means to investigate the effects of CHIT1 overexpression in the context of atherosclerosis.In vitro, CHIT1 overexpression by murine macrophages enhanced protein expression of IL-4, IL-8, and G-CSF by BMDM upon stimulation with a combination of lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). Phosphorylation of ERK1/2 and Akt was also down regulated when exposed to the same inflammatory stimuli. Hyperlipidemic,Ldlr(-/-)-CHIT1-Tg (CHIT1-OE) mice were fed a high-fat diet for 12 weeks in order to study CHIT1 overexpression in atherosclerosis. Although plaque size and lesion area were not affected by CHIT1 overexpressionin vivo, the content of hyaluronic acid (HA) and collagen within atherosclerotic plaques of CHIT1-OE mice was significantly greater. Localization of both ECM components was markedly different between groups. Conclusions These data demonstrate that CHIT1 alters cytokine expression and signaling pathways of classically activated macrophages.In vivo, CHIT1 modifies ECM distribution and content in atherosclerotic plaques, both of which are important therapeutic targets.

Tumor antigen-primed CD8 T cells differentiate into effector T cells that kill tumor cells rapidly, whereas durable responses of CD8 T cells are required to cope with long-lasting tumor growth. However, it is not well known how persisting CD8 T cells are generated. In this study, we analyzed CD8 T cells primed by antigens in tumor-draining lymph nodes and found that CD8 T cells first differentiated into a CD62L-intermediate (CD62L(int)) stage upon antigen stimulation. These cells gave rise to tumor-infiltrating CD62L(-)CD44(high)Bcl6(-)effector T cells and CD62L(+)CD44(high)Bcl6(+)memory-like T cells. Memory-like T cells within the tumor expressed CD127, CXCR3 and had the potential to proliferate significantly when they were transferred into tumor-bearing mice. Bcl6 expression in these T cells was critical because Bcl6(-/-)CD62L(+)CD44(high)CD8T cells within the tumor were defective in expansion after secondary transfer. Taken together, our findings show that CD62L(+)CD44(high)Bcl6(+)cells are generated from highly proliferating CD62L(int)T cells and retain high proliferative potential, which contributes to replenishment of effector T cells within the tumor.